The present invention relates to the use of cytidine diphospho (CDP) compounds as therapeutic agents for preventing phospholipid degradation, and to compositions containing these compounds.
During investigative studies of CDP-choline and CDP-ethanolamine we discovered that injections of these compounds into normal rat brains increased the radioactivity of cerebral lipids when [.sup.14 C]-linoleic acid was present. These results were interpreted to mean that these CDP compounds could stimulate the incorporation of free fatty acids into cerebral lipids. Since prior work had disclosed that ischemic trauma, such as seen in stroke or heart disease, resulted in free fatty acid proliferation, studies were undertaken to determine the effects of CDP compounds on fatty acid concentrations during cerebral ischemia.
Heretofore, Cohadon et al, "Oedeme Cerebral Vasogenique", La Nouvelle Press Medicale, Vol. 8, No. 19, pp 1589-1591 (Apr. 28, 1979) and "Unilateral Brain Injury in the Rabbit: Reversible and Irreversible Damage of the Membranal ATPases", J. Neurochem., 27, 535-541 (1979), report that during vasogenic cerebral edema there is an impairment of mitochondrial ATPase and of Na/K/ATPase. This impairment is speculated to be related to the phospholipid environment in the brain. Use of CDP-choline is noted to be mildly capable of correcting this impairment and in reducing the edema. The CDP-choline was administered by intravenous injection 24 hours after a cold injury was inflicted. Studies by Boismare et al, "Action of Cytidine Diphosphocholine On Functional and Hemodynamic Effects of Cerebral Ischemia in Cats," Pharmacology, 17:15-20 (1978), on cats that were made hypercapnic and acidotic by strangulation, noted that the ampitude of electrical activity increased more with an intracarotid injection of CDP-choline than without such injection. These authors hypothesize that a metabolic action is exhibited by the drug. In other studies of CDP-choline, Manaka et al, "Mechanism of Action of CDP-choline in Parkinsonism", Experientia, 30, pp 179-180 (1974), report that CDP-choline appears to be effective in treating Parkinsonism. Note also that studies on the interaction and effect of CDP-choline on various neurotransmitters have been reported by Martinet et al, "Interaction of CDP-choline with Synaptosonal Transport of Biogenic Amines and Their Precursors in Vitro and In Vivo in the Rat Corpus Striatum", Experientia, 34, pp 1197-1199 (1978) and "Effects of Cytidine-5' Diphosphocholine in Norepinephrine, Dopamine and Serotonin Synthesis in Various Regions of the Rat Brain", Arch. Int. Pharmacodyn, 239, pp 52-61 (1979).